Sucralose (4,1′,6′-trichloro-4,1′,6′-trideoxygalactosucrose), a high-intensity sweetener that can be used in many food and beverage applications, is a galacto-sucrose having the following molecular structure:

Sucralose is made from sucrose by converting the hydroxyls in the 4, 1′ and 6′ positions to chloro groups. In this process, the stereochemical configuration at the 4 position is inverted.
In one process for making sucralose from sucrose, sucrose is first converted to a sucrose-6-ester, such as sucrose-6-acetate or sucrose-6-benzoate. The sucrose-6-ester is chlorinated by reaction with a chlorination agent and a tertiary amide, and the resulting reaction mixture heated and then quenched with aqueous alkali. The resulting 4,1′,6′-trichloro-4,1′,6′-trideoxygalactosucrose ester (sucralose-6-ester) is converted to sucralose, which is subsequently purified and isolated.
Sankey, U.S. Pat. No. 5,470,969; Vernon, EP 0 475 619; Clark, U.S. Pat. No. 6,939,962; and White, EP 0 776 903, the disclosures of which are all incorporated herein by reference, disclose processes for the synthesis of a sucrose-6-ester. The process disclosed by Clark comprises: (a) reacting sucrose in a polar aprotic solvent, such as N,N-dimethyl formamide, with an organotin-based acylation promoter, while continuously adding a non-polar co-solvent capable of removing water by co-distillation, and removing water by co-distillation, to afford a reaction mixture which is substantially free from water, followed by (b) adding a carboxylic anhydride to the reaction mixture and maintaining the resulting reaction mixture at a temperature and for a period of time sufficient to produce a sucrose-6-ester. The non-polar co-solvent is typically a hydrocarbon, such as cyclohexane, n-heptane, toluene, or isooctane.
This process requires large amounts of the non-polar co-solvent, which must be dried before addition and then recovered and re-dried for reuse. Step (a) operates in a temperature region in which decomposition of carbohydrates may occur—even with relatively short reaction times of 20-30 minutes. Because the non-polar co-solvent can cause precipitation of sucrose, the maximum sucrose concentration that can be used in the process is limited by the presence of the non-polar co-solvent. In addition, unreacted sucrose remaining in the sucrose-6-ester product can produce undesirable and difficult to remove tetra-chlorinated species in the subsequent chlorination step. Therefore, a need exists for a process for forming a sucrose-6-ester from sucrose that does not have these disadvantages.
Micinski, PCT Patent Application Publication No. WO2008/084197, discloses a process for the synthesis of a sucrose-6-ester comprising: (a) forming a first reaction mixture comprising sucrose, a polar aprotic solvent, such as N,N-dimethyl formamide, and an organotin-based acylation promoter; (b) removal of water from said first reaction mixture by contacting, in a continuous counter-current manner, with gas or solvent vapour capable of removing water at a temperature, pressure and residence time sufficient to afford a second reaction mixture which is substantially free from water; followed by (c) adding a carboxylic anhydride to said second reaction mixture to afford a third reaction mixture, and maintaining said third reaction mixture at a temperature and for a period of time sufficient to produce a sucrose-6-ester.
This process requires the use of a gas or solvent vapour capable of removing water. According to the present invention, it has been unexpectedly found that use of a gas or solvent vapour capable of removing water is not necessary, and a simpler process has been achieved.